The human skin consists of two major layers, the bottom thicker layer, dermis and the top thinner layer the epidermis. Dermis is the layer which provides the strength, elasticity and the thickness to the skin. With aging, the thickness of the dermal layer is reduced and this is believed to be partially responsible for the formation of wrinkles in aging skin. The top layer of human skin or the epidermis which provides the resilience and the barrier properties of the skin, is composed of many different cell types. Keratinocytes are the major cell type of the epidermis (75-80% of the total number of cells in the human epidermis). Within the epidermis the keratinocytes reside in four distinct stages of differentiation. Epidermal differentiation is important for providing the essential function of the skin, namely to provide a protective barrier against the outside environment and to prevent loss of water from the body. Formation of the cornified envelope is the final stage of keratinocyte differentiation. The enzyme responsible for the formation of cornified envelopes, transglutaminase is a marker of epidermal differentiation. Agents which increase the thickness of the dermal layer and increase the differentiation of keratinocytes in the epidermal layer should therefore be ideal compounds for providing skin conditioning and anti-aging benefits.
Estrogens and synthetic compounds which act like estrogens are known to increase the thickness of the dermal layer and reduce wrinkle formation in the aging skin. Changes in the skin such as skin dryness, loss of skin elasticity and plumpness occurring after menopause are attributed to the lack of estrogen production. Estrogen therapy prevents or slows down many of the changes associated with aging skin (Creidi et al., Effect of a conjugated oestrogen cream (Premarin.RTM.) on aging facial skin, Maturitas, 19, p.211-23, 1994). A synthetic estrogen, diethyl stilbestrol, has the following structure: ##STR1##
This structure is very different from the structure of natural estrogen, estradiol: ##STR2##
In recent years, phytoestrogens (i.e., natural compounds which have estrogen-like activity and which are found in plants) have been increasingly used for therapeutic purposes. Some of the uses described are as hypocholesterolemic and antiatherogenic agents, treatment of cardiovascular diseases especially in postmenopausal women, treatment for osteoporosis in the elderly and as an anticancer agent especially against breast cancer, endometrial and cervical cancer in women (Knight et al., Phytoestrogens--a short review, Maturitas, 22: 167-75, 1995).
The consumer demand for "natural" based products has been growing in recent years. The consumers perceive chemical synthesis as environmentally unsafe. A chemically synthesized ingredient may contain harsh chemicals. Natural products are perceived as pure and mild and superior to chemically synthesized products. However, delivering a cosmetic benefit from plant sources is not trivial. In order to derive a real benefit from a "natural" source a specific active in the plant has to be identified which truly delivers a cosmetic benefit.
One known phytoestrogen is photoanethole: ##STR3##
Photoanethole has not been described for topical or cosmetic use.
The present invention is based at least in part on the discoveries that resveratrol is a phytoestrogen, that it inhibits keratinocyte proliferation, increases keratinocyte differentiation, inhibits melanin production by the skin cells, and alleviates irritation or sting potentially associated with the use of alpha-hydroxy acids.
Resveratrol is a compound found in a variety of plants. Isolation and characterization of resveratrol have been described from a variety of plants such as the roots of Japanese knotweed (Powell et al., Phytochemistry 35, p.335, 1994), from wine and grapes (Goldberg et al; J. Agric. Food Chem., 43, p.1820, 1995 and Cellotti et al., "Resveratrol content of some wines obtained from dried Valpolicella grapes: Recioto and Amarone., J chromatogr A (Netherlands) 730: 47-52,1996), and from peanut plant cultures (Kindl et al., U.S. Pat. No. 5,391,724). Red grapes and red wine contain high amounts of resveratrol and this compound is claimed as one of the reasons for cardiovascular health in wine drinkers. In addition, resveratrol has been shown to be a potent cancer chemopreventive agent and an anti-inflammatory agent. Resveratrol has also been reported to induce differentiation of human promyelocytic leukemia cells (Jang et al., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes, Science 275: 218-220, 1997). Jang et al describe resveratrol's use as an anticancer agent against carcinogen-treated mouse skin cells in culture.
Cosmetic compositions containing grape extract have been described. See for instance abstract of Japanese patent application 06336421 ("JP '421"), disclosing the use of 0.5% grape extract in cosmetic compositions. Scafildi et al. (U.S. Pat. No. 5,683,683) and Zabotto et al. (U.S. Pat. No. 5,439,672) disclose cosmetic compositions containing grape seed oil. Griat et al. (U.S. Pat. No. 5,171,577) disclose cosmetic foams containing cosmetic pips. None of these disclosures, except JP '421, mentions any amount of the grape to be used. JP '421 teaches the presence of 0.5% of grape extract. According to Agricultural Research Service of the United States Department of Agriculture, resveratrol concentration in whole berries is about 15 ppm. Then, the resveratrol concentration in 0.5% grape seed extract is 0.33 micromolar or 0.0000075 wt. %.
The art discussed above does not describe the use of resveratrol for skin care or cosmetic use, does not teach that resveratrol is a phytoestrogen, or that it inhibits keratinocyte proliferation, or that it promotes differentiation of keratinocytes, or that it affects melanin production by the skin cells, or that it controls skin irritation caused by alpha-hydroxy acids.